Recent evidence obtained in our laboratory suggests that a 22,000 molecular weight protein of the cardiac sarcoplasmic reticulum (SR) mediates part of the mechanical response of the mammalian myocardium to inotropic agents such as epinephrine. Abbreviation of systole or increased rate of relaxation after epinephrine administration may be accounted for by an increased rate of removal of calcium from the contractile proteins as a result of increased transport of calcium into the SR. We have previously demonstrated that (1) cyclic AMP-dependent protein kinase catalyzes the phosphoryation of a 22,000 dalton protein and (2) phosphorylation is closely correlated with an increase in calcium pump activity of the cardiac SR. During the present grant year, ongoing studies of the biochemical characterization of the 22,000 dalton protein of cardiac SR will be continued. A possible role of this protein in regulating calcium release from calcium loaded SR vesicles will be explored.